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公开(公告)号:US06277963B1
公开(公告)日:2001-08-21
申请号:US08932787
申请日:1997-09-18
IPC分类号: C07K1640
CPC分类号: G01N33/5041 , C12N9/12 , C12Q1/485 , G01N33/5008 , G01N33/573 , G01N2333/9121 , G01N2500/00
摘要: The present invention relates to a newly identified family of protein serine/threonine kinases which phosphorylate microtubule-associated protein 2 (MAP2). It is based, in part, on the cloning and characterization of novel MAP2 kinases designated extracellular signal-regulated kinase 1, 2, and 3 (ERK1, ERK2, ERK3) which are expressed in the central nervous system, and on the identification of another ERK family member, ERK4, with antisera. The present invention provides for recombinant nucleic acid molecules and proteins representing members of the MAP2 kinase family, and also for microorganisms, transgenic animals, and cell lines comprising recombinant MAP2 kinase molecules. In additional embodiments of the invention, the present invention provides for methods for assaying cellular factor activity, including, but not limited to, nerve growth factor activity, in which the activation of MAP2 kinase serves as an indicator of cellular factor activity. These methods may be extremely useful in screening compounds for the presence of a desired cellular factor activity. In specific embodiments, compounds which may be useful in the treatment of Alzheimer's disease, peripheral neuropathies, and diabetes may be identified using the methods of the invention.
摘要翻译: 本发明涉及磷酸化微管相关蛋白2(MAP2)的新鉴定的蛋白丝氨酸/苏氨酸激酶家族。 它部分地基于在中枢神经系统中表达的称为细胞外信号调节激酶1,2和3(ERK1,ERK2,ERK3)的新型MAP2激酶的克隆和表征,以及鉴定另一种 ERK家族成员,ERK4,具有抗血清。 本发明提供了代表MAP2激酶家族成员的重组核酸分子和蛋白质,还提供了包含重组MAP2激酶分子的微生物,转基因动物和细胞系。 在本发明的另外的实施方案中,本发明提供了测定细胞因子活性的方法,包括但不限于神经生长因子活性,其中MAP2激酶的活化用作细胞因子活性的指标。 这些方法在筛选化合物中以期存在所需的细胞因子活性可能是非常有用的。 在具体实施方案中,可以使用本发明的方法鉴定可用于治疗阿尔茨海默氏病,周围神经病和糖尿病的化合物。
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公开(公告)号:US06277593B1
公开(公告)日:2001-08-21
申请号:US09167874
申请日:1998-10-07
申请人: David M. Valenzuela , Nancy Y. Ip , Henryk D. Cudny , George D. Yancopoulos , Richard M. Harland , William C. Smith , Teresa Lamb , Anne Knecht
发明人: David M. Valenzuela , Nancy Y. Ip , Henryk D. Cudny , George D. Yancopoulos , Richard M. Harland , William C. Smith , Teresa Lamb , Anne Knecht
IPC分类号: C12P2102
CPC分类号: C07K16/22 , A61K38/00 , A61K39/00 , C07K14/475
摘要: Novel dorsal growth inducing factors, complexes including the factors, and DNA or RNA coding sequences for the factors are described.
摘要翻译: 描述了新的背生长诱导因子,包括因子的复合物,以及因子的DNA或RNA编码序列。
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公开(公告)号:US5879672A
公开(公告)日:1999-03-09
申请号:US348492
申请日:1994-12-02
IPC分类号: C12N15/12 , A61K38/00 , A61K38/17 , A61P43/00 , C07K14/47 , C07K14/515 , C07K16/28 , C12N5/02 , C12N5/07 , C12N15/85 , C12P21/00 , A61K38/19 , C07K14/52
CPC分类号: C07K14/515 , A61K38/00 , C07K2319/00
摘要: The present invention provides for an isolated nucleic acid molecule encoding human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds human TIE-2 ligand. The invention also provides an antibody which specifically binds human TIE-2 ligand. The invention further provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization and a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor.
摘要翻译: 本发明提供了编码人TIE-2配体的分离的核酸分子。 此外,本发明提供了特异性结合人TIE-2配体的受体体。 本发明还提供了特异性结合人TIE-2配体的抗体。 本发明进一步提供治疗组合物以及阻断血管生长的方法,促进新生血管形成的方法和促进表达TIE-2受体的细胞的生长或分化的方法。
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公开(公告)号:US5814478A
公开(公告)日:1998-09-29
申请号:US644271
申请日:1996-05-10
IPC分类号: C12N15/09 , A61K31/00 , A61K38/00 , A61K48/00 , A61P21/00 , C07K14/705 , C07K14/78 , C07K14/81 , C07K16/38 , C07K16/40 , C12N1/19 , C12N1/21 , C12N5/10 , C12N9/12 , C12N15/12 , C12P21/08 , C12R1/19 , C12R1/84 , G01N33/53 , G01N33/566 , C12P21/06
CPC分类号: C07K14/78 , C07K14/70567 , C07K14/70571 , C07K14/811 , C07K16/38 , A61K38/00 , A61K48/00
摘要: The present invention provides for a gene, designated as musk, that encodes a novel tyrosine kinase receptor expressed in high levels in denervated muscle. The invention also provides for an isolated and purified polypeptide which activates MuSK receptor. The invention further provides for a polypeptide which is functionally equivalent to the MuSK activating polypeptide. The invention also provides assay systems that may be used to detect and/or measure ligands that bind the musk gene product. The present invention also provides for diagnostic and therapeutic methods based on molecules that activate MuSK.
摘要翻译: 本发明提供了一种称为麝香的基因,其编码在去神经支配的肌肉中以高水平表达的新型酪氨酸激酶受体。 本发明还提供活化MuSK受体的分离和纯化的多肽。 本发明进一步提供功能上等同于MuSK激活多肽的多肽。 本发明还提供可用于检测和/或测量结合麝香基因产物的配体的测定系统。 本发明还提供了基于激活MuSK的分子的诊断和治疗方法。
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公开(公告)号:US5595904A
公开(公告)日:1997-01-21
申请号:US176620
申请日:1994-01-03
IPC分类号: C12N1/21 , C12N9/12 , C12N15/09 , C12N15/54 , C12P21/08 , C12Q1/02 , C12Q1/48 , C12R1/19 , C12R1/91 , G01N33/50 , G01N33/573 , C12N5/00
CPC分类号: G01N33/5041 , C12N9/12 , C12Q1/485 , G01N33/5008 , G01N33/573 , G01N2333/9121 , G01N2500/00
摘要: The present invention relates to a newly identified family of protein serine/threonine kinases which phosphorylate microtubule-associated protein 2 (MAP2). It is based, in part, on the cloning and characterization of novel MAP2 kinases designated extracellular signal-regulated kinase 1, 2, and 3 (ERK1, ERK2, ERK3) which are expressed in the central nervous system, and on the identification of another ERK family member, ERK4, with antisera. The present invention provides for recombinant nucleic acid molecules and proteins representing members of the MAP2 kinase family, and also for microorganisms, transgenic animals, and cell lines comprising recombinant MAP2 kinase molecules. In additional embodiments of the invention, the present invention provides for methods for assaying cellular factor activity, including, but not limited to, nerve growth factor activity, in which the activation of MAP2 kinase serves as an indicator of cellular factor activity. These methods may be extremely useful in screening compounds for the presence of a desired cellular factor activity. In specific embodiments, compounds which may be useful in the treatment of Alzheimer's disease, peripheral neuropathies, and diabetes may be identified using the methods of the invention.
摘要翻译: 本发明涉及磷酸化微管相关蛋白2(MAP2)的新鉴定的蛋白丝氨酸/苏氨酸激酶家族。 其部分基于在中枢神经系统中表达的命名为细胞外信号调节激酶1,2和3(ERK1,ERK2,ERK3)的新型MAP2激酶的克隆和表征,以及鉴定另一种 ERK家族成员,ERK4,具有抗血清。 本发明提供了代表MAP2激酶家族成员的重组核酸分子和蛋白质,还提供了包含重组MAP2激酶分子的微生物,转基因动物和细胞系。 在本发明的另外的实施方案中,本发明提供了测定细胞因子活性的方法,包括但不限于神经生长因子活性,其中MAP2激酶的活化用作细胞因子活性的指标。 这些方法在筛选化合物中以期存在所需的细胞因子活性可能是非常有用的。 在具体实施方案中,可以使用本发明的方法鉴定可用于治疗阿尔茨海默氏病,周围神经病和糖尿病的化合物。
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公开(公告)号:US08847004B2
公开(公告)日:2014-09-30
申请号:US13372787
申请日:2012-02-14
申请人: Andrew J. Murphy , Sean Stevens , Chozhavendan Rathinam , Elizabeth Eynon , Markus Manz , Richard Flavell , George D. Yancopoulos
发明人: Andrew J. Murphy , Sean Stevens , Chozhavendan Rathinam , Elizabeth Eynon , Markus Manz , Richard Flavell , George D. Yancopoulos
IPC分类号: A01K67/027
CPC分类号: A01K67/0278 , A01K67/027 , A01K67/0271 , A01K2207/12 , A01K2207/15 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/03 , A01K2267/0337 , A61K49/0008 , C12N15/8509 , C12N2015/8536 , G01N33/5088 , G01N2500/10
摘要: Genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein are provided. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that have been engrafted with human cells such as human hematopoietic cells, and methods for making such engrafted mice. These mice find use in a number of applications, such as in modeling human immune disease and pathogen infection; in in vivo screens for agents that modulate hematopoietic cell development and/or activity, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to hematopoietic cells; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on hematopoietic cells; in in vivo screens of human hematopoietic cells from an individual to predict the responsiveness of an individual to a disease therapy, etc.
摘要翻译: 提供了包含编码人M-CSF蛋白的核酸序列的转基因小鼠。 还提供了包含编码人类细胞如人类造血细胞的人M-CSF蛋白质的核酸序列的遗传修饰的小鼠,以及用于制备这种移植的小鼠的方法。 这些小鼠可用于许多应用,例如建模人类免疫疾病和病原体感染; 在用于调节造血细胞发育和/或活性的试剂的体内筛选中。 处于健康或疾病状态; 在对造血细胞有毒性的药物的体内筛选中; 在体内筛选用于防止,减轻或逆转毒性剂对造血细胞的毒性作用的药剂; 在来自个体的人类造血细胞的体内筛选中以预测个体对疾病治疗的反应性等。
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公开(公告)号:US08647842B2
公开(公告)日:2014-02-11
申请号:US13439889
申请日:2012-04-05
CPC分类号: C07K14/71 , A61K38/00 , C07K16/22 , C07K19/00 , C07K2319/00 , C07K2319/30
摘要: The present invention provides methods for producing a fusion protein capable of binding vascular endothelial cell growth factor (VEGF). The methods of the invention comprise growing recombinant cells in suspension culture, wherein the recombinant cells contain an expression vector comprising a nucleic acid molecule encoding a fusion protein that binds VEGF, and isolating the fusion protein from the suspension culture. The fusion protein may comprise a VEGF receptor component having an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor, an Ig domain 3 of a second VEGF receptor, and a multimerizing component.
摘要翻译: 本发明提供了能够结合血管内皮细胞生长因子(VEGF)的融合蛋白的方法。 本发明的方法包括在悬浮培养物中培养重组细胞,其中重组细胞含有包含编码融合蛋白的核酸分子的表达载体,所述融合蛋白与VEGF结合,并从融合蛋白与悬浮培养物分离。 融合蛋白可以包含具有第一VEGF受体的免疫球蛋白样(Ig)结构域2,第二VEGF受体的Ig结构域3和多聚化成分的VEGF受体组分。
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公开(公告)号:US20140017782A1
公开(公告)日:2014-01-16
申请号:US14036865
申请日:2013-09-25
IPC分类号: C12N15/85
摘要: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
摘要翻译: 一种用于工程化和利用大型DNA载体通过同源重组靶向并以任何所需方式修饰真核细胞中的内源基因和染色体基因座的方法。 用于真核细胞的这些大的DNA靶向载体,称为LTVEC,衍生自克隆基因组DNA的片段,大于通常用于在真核细胞中进行同源靶向的其它方法通常使用的那些。 还提供了检测真核细胞的快速和方便的方法,其中LTVEC已经正确靶向和修饰了所需的内源基因或染色体基因座(位点),以及使用这些细胞产生具有遗传修饰的生物体。
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公开(公告)号:US20130149744A1
公开(公告)日:2013-06-13
申请号:US13439889
申请日:2012-04-05
IPC分类号: C07K19/00
CPC分类号: C07K14/71 , A61K38/00 , C07K16/22 , C07K19/00 , C07K2319/00 , C07K2319/30
摘要: The present invention provides methods for producing a fusion protein capable of binding vascular endothelial cell growth factor (VEGF). The methods of the invention comprise growing recombinant cells in suspension culture, wherein the recombinant cells contain an expression vector comprising a nucleic acid molecule encoding a fusion protein that binds VEGF, and isolating the fusion protein from the suspension culture. The fusion protein may comprise a VEGF receptor component having an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor, an Ig domain 3 of a second VEGF receptor, and a multimerizing component.
摘要翻译: 本发明提供了能够结合血管内皮细胞生长因子(VEGF)的融合蛋白的方法。 本发明的方法包括在悬浮培养物中培养重组细胞,其中重组细胞含有包含编码融合蛋白的核酸分子的表达载体,所述融合蛋白与VEGF结合,并从融合蛋白与悬浮培养物分离。 融合蛋白可以包含具有第一VEGF受体的免疫球蛋白样(Ig)结构域2,第二VEGF受体的Ig结构域3和多聚化成分的VEGF受体组分。
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公开(公告)号:US08158581B2
公开(公告)日:2012-04-17
申请号:US12894278
申请日:2010-09-30
CPC分类号: C07K14/65 , A61K38/30 , C07K2319/00 , C07K2319/30 , C07K2319/75
摘要: A fusion protein comprising at least one IGF1 variant component and a fusion component (F), and, optionally, a signal sequence, exhibits improved stability relative to the native IGF1 or IGF2 polypeptide. The fusion component (F) may be a multimerizing component, such as an immunoglobulin domain, in particular, the Fc domain of IgG or a heavy chain of IgG. IGF1 variants were shown to have improved ability to increase muscle mass in a subject suffering from muscle atrophy caused by cachexia, immobilization, aging, chronic disease, cancer, hereditary condition, an atrophy-causing agent, and the like. IGF1 variants are also effective in decreasing blood glucose in a subject suffering from diabetes or hyperglycemia.
摘要翻译: 包含至少一种IGF1变体组分和融合组分(F)以及任选的信号序列的融合蛋白相对于天然IGF1或IGF2多肽表现出改进的稳定性。 融合组分(F)可以是多聚化组分,例如免疫球蛋白结构域,特别是IgG的Fc结构域或IgG的重链。 IGF1变体显示具有改善的能力,以增加受到恶病质,固定化,老化,慢性疾病,癌症,遗传性疾病,引起萎缩症等引起的肌肉萎缩的受试者的肌肉质量的增加。 IGF1变体在降低患有糖尿病或高血糖症的受试者中的血糖中也是有效的。
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